title: Comparison of ceftaroline fosamil, daptomycin and tigecycline in an experimental rabbit endocarditis model caused by methicillin-susceptible, methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus.
abstract: OBJECTIVE
  The aim of this study was to compare the in vivo activities of the new antistaphylococcal drugs ceftaroline fosamil, daptomycin and tigecycline at projected human therapeutic doses against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains in a rabbit model of endocarditis.
  
  
  METHODS
  The efficacy of therapeutic regimens in our model was evaluated following 4 days of treatment by determining colony counts of infected vegetations. Emergence of resistant variants during therapy was assessed.
  
  
  RESULTS
  Using this model of infective endocarditis, ceftaroline fosamil and daptomycin demonstrated high bactericidal in vivo activity (reduction of >5 log(10) cfu/g of vegetation) after a 4 day treatment against MSSA, MRSA and GISA strains. Both drugs were more efficacious than tigecycline, which showed moderate activity but failed to exhibit a bactericidal effect. Ceftaroline was superior to daptomycin in terms of sterilization of the vegetations. Emergence of resistant variants during daptomycin therapy was observed in two animals (one in the MSSA group and one in the MRSA group) but was not observed in ceftaroline- or tigecycline-treated animals.
  
  
  CONCLUSIONS
  The novel β-lactam agent ceftaroline fosamil was the most active bactericidal drug in this model and is a promising therapeutic option for the treatment of severe S. aureus infections, including those caused by MRSA and GISA strains.
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Thérapeutiques Cliniques et Expérimentales des Infections, EA3826, F-44000 Nantes, France. cedric.jacqueline@univ-nantes.fr
authors.forename: Cédric
authors.initials: C
authors.lastname: Jacqueline
authors.forename: Gilles
authors.initials: G
authors.lastname: Amador
authors.forename: Eric
authors.initials: E
authors.lastname: Batard
authors.forename: Virginie
authors.initials: V
authors.lastname: Le Mabecque
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Miègeville
authors.forename: Donald
authors.initials: D
authors.lastname: Biek
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.forename: Gilles
authors.initials: G
authors.lastname: Potel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002511:Cephalosporins / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D050296:Microbial Viability / Q000187:drug effects; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011817:Rabbits; D012376:Rodent Diseases / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000078304:Tigecycline; D016896:Treatment Outcome; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017576:Daptomycin; D008911:Minocycline; D000078304:Tigecycline; D000097583:Ceftaroline